Cardiovascular diseases are the major cause of morbidity and mortality in diabetic patients, involving cardiac tissues as well as large vessels in the brain, heart, and lower extremities (1). In the heart, the majority of the cardiac failure is probably due to atherosclerotic processes in the coronary vessels, but multiple studies have documented that a sizeable number of diabetic patients suffer from congestive heart failure without significant coronary disease (2, 3). In addition, type I diabetic patients with &lt;5 yr of disease have been reported to have abnormal cardiac function in the absence of significant coronary vessel disease (4). These clinical findings are supported further by animal studies documenting biochemical and functional changes in the cardiac tissue shortly after induction of diabetes (5-8). From these results, it has been postulated that diabetes mellitus and its metabolic sequelae can induce a specific form of cardiomyopathy (8, 9).
As with other chronic complications of diabetes, the cardio-vascular changes once established are difficult to reverse, both in clinical and experimental settings (10-12). Most cardiovascular abnormalities are metabolically induced with a great deal of interest directed towards identifying alterations in gene expression induced by diabetes or hyperglycemia in the vasculature. Since thickening of basement membrane is a classical finding in diabetes microvasculature (10), many of the studies concerning glucose-regulated genes have primarily focused on changes in the basement matrix components using cultured vascular cells (13, 14).